title: Stress-induced alterations in anxiety-like behavior and adaptations in plasticity in the bed nucleus of the stria terminalis.
abstract: In vulnerable individuals, exposure to stressors can result in chronic disorders such as generalized anxiety disorder (GAD), major depressive disorder (MDD), and post-traumatic stress disorder (PTSD). The extended amygdala is critically implicated in mediating acute and chronic stress responsivity and anxiety-like behaviors. The bed nucleus of the stria terminalis (BNST), a subregion of the extended amygdala, serves as a relay of corticolimbic information to the paraventricular nucleus of the hypothalamus (PVN) to directly influence the stress response. To investigate the influence of the corticosteroid milieu and housing conditions on BNST function, adult C57Bl/6J were either acutely or chronically administered corticosterone (CORT, 25mg/kg in sesame oil) or vehicle (sesame oil) or were group housed or socially isolated for 1 day (acute) or 6-8 weeks (chronic). To ascertain whether these stressors could influence anxiety-like behavior, studies were performed using the novel open-field (NOF) and the elevated zero maze (EZM) tests. To investigate potential associated changes in plasticity, alterations in BNST function were assessed using ex vivo extracellular field potential recordings in the (dorsal-lateral) dlBNST and a high frequency stimulus protocol to induce long-term potentiation (LTP). Our results suggest that chronic CORT injections and chronic social isolation housing conditions lead to an increase in anxiety-like behavior on the EZM and NOF. Chronically stressed mice also displayed a parallel blunting of LTP in the dlBNST. Conversely, acute social isolation housing had no effect on anxiety-like behavior but still resulted in a blunting of LTP in the dlBNST. Collectively, our results suggest acute and chronic stressors can have a distinct profile on plasticity in the BNST that is not uniformly associated with an increase in anxiety-like behavior.
authors.affiliation: Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232-0615, USA. Kelly.l.conrad@vanderbilt.edu
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Conrad
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Louderback
authors.forename: Caitlin P
authors.initials: CP
authors.lastname: Gessner
authors.forename: Danny G
authors.initials: DG
authors.lastname: Winder
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000209:etiology* / Q000473:pathology*; D001522:Behavior, Animal / Q000187:drug effects; D001703:Biophysics; D003345:Corticosterone / Q000009:adverse effects; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018408:Patch-Clamp Techniques / Q000379:methods; D012686:Septal Nuclei / Q000187:drug effects / Q000503:physiopathology*; D012934:Social Isolation / Q000523:psychology; D013997:Time Factors
chemical_list: D003345:Corticosterone